Healthcare-associated infections (HAIs) increase patient morbidity and mortality. The transmission of bacteria and viruses is an area that needs further study. Our group has over 160 publications in the area of healthcare-associated infections, with over 40 publications in the application focus of transmission of infectious pathogens and identification of novel strategies to improve the effectiveness of personal protective equipment. We have translated numerous T0 results into T2 studies to prevent transmission of infectious pathogens. We have experience developing and implementing multi-site studies across the spectrum of healthcare. We have had over 16 grants funded by CDC, NIH, VA and AHRQ to study optimal methods to prevent the transmission of bacterial pathogens. We have successfully performed nine multi-center studies across over 50 institutions in 32 states. We also had a project with the Maryland state health department that we led involving 40 facilities including 30 acute care facilities and 10 long-term care facilities. Thus, we believe we are well-qualified to be chosen to be a member of the CDC Prevention Epicenters for the Prevention of Healthcare Associated Infections. Our aims directly address the funding announcement; they are: Aim 1: Perform a multi-site intensive-care unit (ICU) cohort study to determine which patient risk factors, including comorbid conditions and severity of illness markers, and which healthcare worker-patient interactions lead to greater transmission of carbapenem-resistant Enterobacteriaceae (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). Aim 2: Using an existing cohort of residents from community-based nursing homes in two states, estimate the overall transmission risk for resistant Gram-negative bacteria, as well as which patient risk factors and healthcare activities lead to greater transmission. Aim 3: Perform a randomized non-inferiority trial to determine if using an alcohol-based hand rub to clean gloved hands when an indication for hand hygiene arises during a single patient encounter is as effective as the current recommendation of changing gloves. Aim 4: Evaluate the effectiveness of practices to decontaminate personal protective equipment (PPE) after use for antibiotic-resistant bacteria and viruses similar to Ebola and Influenza in a laboratory settin.